[Show abstract][Hide abstract]ABSTRACT: The study was designed to verify if one or more electrophysiological parameters could predict a risk of nonrecovery of normal facial function and the development of synkinesis in Bell's palsy (BP) subjects.

[Show abstract][Hide abstract]ABSTRACT: BACKGROUND: Painful neuropathy is associated with plasticity changes in the nervous system. Standard repetitive transcranial magnetic stimulation (rTMS) is a non-invasive technique used to study changes in cortical excitability and to inhibit pain perception. Deep rTMS is a newer development that allows direct activation of deeper neuronal populations, by a unique coil design termed the H-coil. This study was designed to assess whether deep rTMS applied over the motor cortical lower-limb representation relieves pain in patients with diabetic neuropathy. METHODS: Patients were randomly assigned to receive daily real or sham H-coil rTMS for 5 consecutive days. After a 5-week washout period, they crossed over to the alternative treatment for additional 5 days (according to a crossover study design). Outcome measures were changes in the visual analogue scale (VAS) for pain and in area and threshold of RIII nociceptive flexion reflex (RIII reflex). RESULTS: Of the 25 patients randomized, 23 completed the study. After real rTMS, the VAS scores decreased significantly (p = 0.01), and so did RIII reflex area (p < 0.01), while no significant effects in these variables were induced by the sham rTMS treatment. The rTMS-induced changes in the outcome measures disappeared about 3 weeks after stimulation. All patients tolerated stimulation well. CONCLUSIONS: Deep H-coil rTMS provides pain relief in patients with diabetic neuropathy. This innovative technique can induce a therapeutic effect on brain areas that otherwise remain difficult to target. rTMS may produce its analgesic effects, inducing motor cortex plasticity and activating descending inhibitory pain control systems.

[Show abstract][Hide abstract]ABSTRACT: In Parkinson's disease (PD) the urinary dysfunction manifests primarily with symptoms of overactive bladder (OAB). The OAB questionnaire (OAB-q) is a measure designed to assess the impact of OAB symptoms on health-related quality of life. In this study, we quantified the urinary symptoms in a large cohort of PD patients by using the OAB-q short form. Possible correlations between the OAB-q and clinical features were tested. Three hundred and two PD patients were enrolled in the study. Correlations between the OAB-q and sex, age, Unified Parkinson's Disease Rating Scale part III (UPDRS-III), Hoehn-Yahr (H-Y) staging, disease duration, and treatment were analyzed. Data were compared with a large cohort of 303 age-matched healthy subjects. The OAB-q yielded significantly higher scores in PD patients than in healthy subjects. In the group of PD patients, all the variables tested were similar between men and women. Pearson's coefficient showed a significant correlation between mean age, disease duration, mean OAB-q scores, UPDRS-III scores, and H-Y staging. A multiple linear regression analysis showed that OAB-q values were significantly influenced by age and UPDRS-III. No statistical correlations were found between OAB-q scores and drug therapy or the equivalent levodopa dose, whilst the items relating to the nocturia symptoms were significantly associated with the equivalent levodopa dose. Our findings suggest that bladder dysfunction assessed by OAB-q mainly correlates with UPDRS-III scores for severity of motor impairment, possibly reflecting the known role of the decline in nigrostriatal dopaminergic function in bladder dysfunction associated with PD and patients' age. Our study also suggests that the OAB-q is a simple, easily administered test that can objectively evaluate bladder function in patients with PD.

[Show abstract][Hide abstract]ABSTRACT: Botulinum toxin type A (BoNT/A) has been proposed as an alternative treatment for sialorrhoea in patients with amyotrophic lateral sclerosis (ALS). In an open-label prospective study, BoNT/A was injected into the parotid glands bilaterally using anatomic landmarks in 26 ALS patients with bulbar symptoms. Two weeks after injection the severity of sialorrhoea and the related disability were evaluated subjectively and objectively. A group of healthy subjects acted as controls for saliva production. Patients also underwent electrophysiological tests to evaluate possible toxin effects in the nearby non-injected muscles by comparing the amplitude of compound motor action potentials (cMAPs) elicited by electrical stimulation and recorded from the orbicularis oculi and masseter muscles. After BoNT/A injections, of the 26 patients treated, 23 reported that the severity of sialorrhoea improved and the disabling symptoms diminished. Cotton roll weight also decreased after BoNT/A injection, suggesting a reduction in saliva production. Two patients complained of dry mouth. BoNT/A injection left the cMAP amplitude unchanged, suggesting that botulinum toxin does not significantly affect the non-injected facial and masticatory muscles. In conclusion, intraparotid anatomically-guided BoNT/A injection is an effective, easy, and safe treatment for sialorrhoea in patients with bulbar symptoms related to ALS.

[Show abstract][Hide abstract]ABSTRACT: To find out more about glutamatergic and gabaergic transmission in migraine, in this study we investigated glutamate-dependent short-term synaptic potentiation and GABA-dependent inhibitory cortical interneuron excitability as assessed by 5Hz-rTMS delivered over primary motor cortex (M1) (motor evoked potential, MEP, amplitude facilitation and cortical silent period, CSP, duration lengthening) in migraine patients with (MA) and without aura (MwoA) and healthy controls. We studied 37 patients with migraine (19 MA and 18 MwoA) and 19 healthy control subjects. 5Hz-rTMS was delivered at 120% resting motor threshold to the hand motor area of the left hemisphere with the target muscle at rest and during contraction. Three of the MA patients were also tested at the end of visual aura during a spontaneous migraine attack. ANOVA showed that the MEP significantly increased in size and CSP significantly lengthened during 5Hz-rTMS in the three groups tested. The 5Hz-rTMS-induced MEP facilitation differed significantly being highest in MA patients. In the three patients tested both ictally and interictally the MEP increased during the interictal session but remained unchanged when the visual aura ended. Our study shows that the neurophysiological feature that differentiates MA patients from MwoA patients and healthy controls is an abnormal M1 susceptibility to 5Hz-rTMS both outside and during the attack suggesting that glutamate-dependent short-term M1 cortical potentiation patterns differ in migraine with and without aura.

[Show abstract][Hide abstract]ABSTRACT: Repetitive transcranial magnetic stimulation (rTMS) delivered in short trains at 5Hz frequency and suprathreshold intensity over the primary motor cortex (M1) in healthy subjects facilitates the motor-evoked potential (MEP) amplitude by increasing cortical excitability through mechanisms resembling short-term synaptic plasticity. In this study, to investigate whether rTES acts through similar mechanisms we compared the effects of rTMS and repetitive transcranial electrical stimulation (rTES) (10 stimuli-trains, 5Hz frequency, suprathreshold intensity) delivered over the M1 on the MEP amplitude. Four healthy subjects were studied in two separate sessions in a relaxed condition. rTMS and anodal rTES were delivered in trains to the left M1 over the motor area for evoking a MEP in the right first dorsal interosseous muscle. Changes in MEP size and latency during the course of the rTMS and rTES trains were compared. The possible effects of muscle activation on MEP amplitude were evaluated, and the possible effects of cutaneous trigeminal fibre activation on corticospinal excitability were excluded in a control experiment testing the MEP amplitude before and after supraorbital nerve repetitive electrical stimulation. Repeated measures analysis of variance (ANOVA) showed that rTES and rTMS trains elicited similar amplitude first MEPs and a similar magnitude MEP amplitude facilitation during the trains. rTES elicited a first MEP with a shorter latency than rTMS, without significant changes during the course of the train of stimuli. The MEP elicited by single-pulse TES delivered during muscle contraction had a smaller amplitude than the last MEP in the rTES trains. Repetitive supraorbital nerve stimulation left the conditioned MEP unchanged. Our results suggest that 5 Hz-rTES delivered in short trains increases cortical excitability and does so by acting on the excitatory interneurones probably through mechanisms similar to those underlying the rTMS-induced MEP facilitation.

[Show abstract][Hide abstract]ABSTRACT: We designed this study to investigate possible correlations between variables measuring primary motor cortex excitability detected by single and paired-pulse transcranial magnetic stimulation (TMS) and the severity of clinical manifestations in patients with multiple sclerosis (MS). Thirty patients with MS in remission, 16 with relapsing-remitting (RR), 14 with secondary progressive disease (SP) and 17 healthy subjects participated in the study. In each subject, the central motor conduction time (CMCT) was calculated, and single-pulse and paired-pulse TMS at 3 and 10 ms interstimulus intervals was delivered over the primary motor cortex of the dominant hemisphere to measure the amplitude of motor-evoked potentials (MEPs), motor threshold (MTh), intracortical inhibition (ICI) and facilitation (ICF). Correlations were determined between the patients' TMS findings and magnetic resonance imaging (MRI) (lesion load) and clinical features (expanded disability status scale, EDSS score). EDSS scores were significantly higher in SPMS than in RRMS patients. The MTh was significantly higher, and the MEP was significantly smaller in SPMS patients than in RRMS patients and control subjects. All patients had longer CMCTs than healthy subjects. In all patients, paired-pulse TMS elicited an inhibited test MEP at the 3-ms ISI and a facilitated test MEP at the 10 ms ISI. Post hoc analysis showed that ICI was significantly lower in SPMS patients than in those with RRMS and healthy subjects. EDSS scores correlated significantly with TMS measures (MEP, ICI, CMCT and MTh), but not with MRI lesion load. It was found that intracortical excitability as measured with TMS differs according to the clinical course of MS; it remains normal in patients with low EDSS scores and is altered in patients with high EDSS scores.

[Show abstract][Hide abstract]ABSTRACT: We designed this study to investigate possible correlations between variables measuring primary motor cortex excitability detected by single and paired-pulse transcranial magnetic stimulation (TMS) and the severity of clinical manifestations in patients with multiple sclerosis (MS). Thirty patients with MS in remission, 16 with relapsing–remitting (RR), 14 with secondary progressive disease (SP) and 17 healthy subjects participated in the study. In each subject, the central motor conduction time (CMCT) was calculated, and single-pulse and paired-pulse TMS at 3 and 10 ms interstimulus intervals was delivered over the primary motor cortex of the dominant hemisphere to measure the amplitude of motor-evoked potentials (MEPs), motor threshold (MTh), intracortical inhibition (ICI) and facilitation (ICF). Correlations were determined between the patients' TMS findings and magnetic reso-nance imaging (MRI) (lesion load) and clinical features (expanded disability status scale, EDSS score). EDSS scores were significantly higher in SPMS than in RRMS patients. The MTh was significantly higher, and the MEP was significantly smaller in SPMS patients than in RRMS patients and control subjects. All patients had longer CMCTs than healthy subjects. In all patients, paired-pulse TMS elicited an inhibited test MEP at the 3-ms ISI and a facilitated test MEP at the 10 ms ISI. Post hoc analysis showed that ICI was significantly lower in SPMS patients than in those with RRMS and healthy subjects. EDSS scores correlated significantly with TMS measures (MEP, ICI, CMCT and MTh), but not with MRI lesion load. It was found that intracortical excitability as measured with TMS differs according to the clinical course of MS; it remains normal in patients with low EDSS scores and is altered in patients with high EDSS scores.

[Show abstract][Hide abstract]ABSTRACT: Allgrove syndrome is a rare autosomal recessive disorder characterised by childhood onset, alacrima, oesophageal achalasia, adrenocortical insufficiency, neurological and occasionally autonomic involvement. Although the disease has been associated with mutations in the ALADIN gene on chromosome 12q13, it is genetically heterogeneous. The case we report is interesting because of its onset in adulthood, long duration of disease and prominent neurological dysfunctions. After the onset of neurological abnormalities the diagnosis went unrecognised for years until the patient presented for evaluation of dysphagia. The presence of achalasia with dysphagia, adrenal insufficiency, reduced tear production, optic atrophy and peripheral motor-sensory neuropathy with axonal loss led us to clinically diagnose Allgrove syndrome even though a genetic study showed no mutations in the ALADIN gene exons. The case we report shares many clinical features with Allgrove syndrome and, even with the limitations of a single case, underlines the variability in this syndrome and the need for appropriate investigations along with a multidisciplinary approach.

[Show abstract][Hide abstract]ABSTRACT: In this study we investigate whether the cutaneous silent period (CSP)-an inhibitory response evoked in hand muscles by painful digital nerve stimulation-is useful for assessing nociceptive pathway function in patients with neuropathic pain. In 40 patients with peripheral neuropathy (21 without and 19 with neuropathic pain) we recorded the CSP in the abductor digiti minimi after fifth digit stimulation and also recorded laser evoked potentials (LEPs) after stimulation applied to the ulnar territory of the hand. Although the LEP amplitude was significantly lower in patients with pain than in those without (P < 0.005), the CSP duration did not differ between groups (P > 0.50). Pain intensity correlated significantly with LEP amplitudes (P < 0.005) but not with CSP duration (P > 0.5). Our findings indicate that the CSP is not useful for assessing nociceptive pathway function in patients with neuropathic pain.

[Show abstract][Hide abstract]ABSTRACT: Although clinical studies show that cannabinoids improve central pain in patients with multiple sclerosis (MS) neurophysiological studies are lacking to investigate whether they also suppress these patients' electrophysiological responses to noxious stimulation. The flexion reflex (FR) in humans is a widely used technique for assessing the pain threshold and for studying spinal and supraspinal pain pathways and the neurotransmitter system involved in pain control. In a randomized, double-blind, placebo-controlled, cross-over study we investigated cannabinoid-induced changes in RIII reflex variables (threshold, latency and area) in a group of 18 patients with secondary progressive MS. To investigate whether cannabinoids act indirectly on the nociceptive reflex by modulating lower motoneuron excitability we also evaluated the H-reflex size after tibial nerve stimulation and calculated the H wave/M wave (H/M) ratio. Of the 18 patients recruited and randomized 17 completed the study. After patients used a commercial delta-9-tetrahydrocannabinol (THC) and cannabidiol mixture as an oromucosal spray the RIII reflex threshold increased and RIII reflex area decreased. The visual analogue scale score for pain also decreased, though not significantly. Conversely, the H/M ratio measured before patients received cannabinoids remained unchanged after therapy. In conclusion, the cannabinoid-induced changes in the RIII reflex threshold and area in patients with MS provide objective neurophysiological evidence that cannabinoids modulate the nociceptive system in patients with MS.

[Show abstract][Hide abstract]ABSTRACT: Repetitive transcranial magnetic stimulation (5 Hz-rTMS, 10 stimuli, 120% resting motor threshold intensity, RMT) produces in healthy subjects a progressive facilitation of motor-evoked potential (MEP) amplitude probably through a short-term enhancement of cortical excitatory interneurones. We had the opportunity to investigate the effect of 5 Hz-rTMS delivered over the right and left primary motor cortex (M1) in a patient with limb-kinetic apraxia of the left hand and fingers and reduced cerebral perfusion in the fronto-parietal cortex of the right hemisphere documented by single-photon emission computed tomography scans. Changes in the MEP size during the trains and the RMT were measured and compared between the hemispheres. 5 Hz-rTMS was also delivered in a group of healthy subjects over both hemispheres in order to compare changes in the MEP size from the right and left M1. In the patient, 5 Hz-rTMS delivered over the left hemisphere elicited normal MEPs that progressively increased in size during the trains whereas 5 Hz-rTMS delivered over the right affected hemisphere failed to facilitate the MEP size. RMT was similar in both hemispheres. In healthy subjects, 5 Hz-rTMS delivered over either hemisphere elicited a similar, significant MEP size facilitation. Despite the limitations of a single case, our findings suggest an altered response to 5 Hz-rTMS over the M1 of the affected hemisphere. This asymmetric response correlated with the altered perfusion in the right hemisphere and the patient's lateralized clinical manifestations of apraxia.